The CAPI 3 Hb A1c kit is intended for separation and quantification of the HbA1c glycated fraction of hemoglobin (in IFCC unit (mmol/mol) and NGSP unit (%)) in venous whole human blood, by capillary electrophoresis in alkaline buffer with the CAPILLARYS 3 TERA instrument of hemoglobin A1c is used as an aid in diagnosis of diabetes, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. The CAPI 3 Hb A1c kit is intended for in vitro Diagnostic Use Only.

Device Description

The CAPILLARYS 3 TERA instrument uses the principle of capillary electrophoresis in free solution. With this technique, charged molecules are separated by their electrophoretic mobility in an alkaline buffer with a specific pH. Separation occurs according to the electrolyte pH and electroosmotic flow. The CAPILLARYS 3 TERA instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses of HbA1c quantification in a whole blood sample. A sample dilution with hemolysing solution is prepared and injected by aspiration at the anodic end of the capillary. A high voltage protein separation is then performed and direct detection of the hemoglobins is made at the cathodic end of the capillary at 415 nm, which is the absorbance wave length specific to hemoglobins. Before each run, the capillaries are washed with a wash solution and prepared for the next analysis with buffer. Direct detection provides accurate relative quantification of individual hemoglobin A1c fraction. In addition, the high resolution of CAPI 3 Hb A1c procedure allows the quantification of HbA1c even in the presence of labile HbA1c. carbamylated and acetylated hemoglobins, and major hemoqlobin variants. By using an alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: A2/C, E, S/D, F, A0, other Hb (including minor Hb A1) and then A1c. The HbA1c concentrations are standardized and indicated in %HbA1c (DCCT/NGSP) and in mmol/mol (IFCC) units.

AI/ML Overview

The provided text describes the 510(k) premarket notification for the CAPI 3 Hb A1c kit, a device used for measuring hemoglobin A1c levels. The document outlines the device's indications for use, technological characteristics, and performance data to demonstrate substantial equivalence to a legally marketed predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The "Special Controls for Diabetes Diagnosis Claim" section (Section 6) explicitly lists the acceptance criteria set by the FDA for devices of this type, along with how the device's performance data addresses these. While the document doesn't present a direct "acceptance criteria vs. reported performance" table, I can synthesize one from Section 6 and the preceding "Performance Data" (Section 5).

Acceptance Criteria and Reported Device Performance for CAPI 3 Hb A1c

Acceptance Criteria (from Section 6)	Reported Device Performance (from Section 5)
1. Standardization verification: Device must have initial and annual standardization verification by certifying glycohemoglobin standardization organization deemed acceptable by FDA.	c. Traceability, Stability (controls, calibrators, or methods): The CAPI 3 Hb A1c test standardization is traceable to the International Federation of Clinical Chemistry (IFCC) reference calibrators. The CAPI 3 Hb A1c assay is NGSP certified. The NGSP certification expires in one year. See the NGSP website for current certification at http://www.ngsp.org.
2. Precision testing: Must use blood samples with concentrations near 5.0%, 6.5%, 8.0%, and 12% hemoglobin A1c. Testing must evaluate precision over a minimum of 20 days using at least 3 lots of the device and instruments, as applicable.	a. Precision / Reproducibility: The precision was evaluated based on CLSI guidelines EP05-A3. Four whole blood samples at targeted HbA1c concentrations of ~5%, ~6.5%, ~8%, and ~12% were used. The study included two quality control materials and two calibrators. Samples analyzed in duplicate on two capillaries per run on 3 instruments. The study used three lots of kits over 24 days, yielding a total of 1728 results over 72 days. The detailed tables (pages 8-12) show SD and CV values per sample (~5.2%, ~6.5%, ~8.1%, ~11.9% NGSP units) across within-capillary, between-capillary, between-run, between-day, between-lot, and between-instrument variability, demonstrating low CVs for all measured components, with total reproducibilities ranging from 1.0% to 2.0% CV (NGSP units).
3. Accuracy testing: Must include a minimum of 120 blood samples that span the measuring interval of the new device and compare results of the new device to results of the standardized method. Results must demonstrate little or no bias versus the standardized method.	e. Comparison Studies: A method comparison study of 152 variant-free whole blood samples covering the measuring range (3.9% - 16.5% HbA1c) was evaluated. Results were compared to testing at an NGSP reference laboratory using the cleared HPLC HbA1c method (Automated Glycohemoglobin Analyzer HLC-712G8). The samples spanned extensively around decision points (e.g., 23% of samples 6.0%-6.5%, 24% from 6.5%-7.0%). Correlation coefficient (r) was 0.999. Slope was 1.014 (95% CI: 1.007 to 1.021). Y-intercept was -0.142 (95% CI: -0.197 to -0.087). Average bias (all samples) was -0.04 (-0.06 to -0.02)%. Bias at 6.5% was -0.05 (-0.07 to -0.03)%. These indicate very low bias and strong correlation.
4. Total error (TE) evaluation: Must be evaluated using single measurements by the new device compared to the results of the standardized test method, and this evaluation must demonstrate a total error of less than or equal to 6%.	f. Total Error Calculations: Total error (TE) was calculated for four concentrations (5.2%, 6.5%, 8.1%, and 11.9% NGSP units) using the formula %TE=
5. Interference testing: Must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.	g. Interferences: Hemoglobin Variant Study was performed using specific samples known to contain hemoglobin variants S, C, E, D, A2, and F. The samples were analyzed with a reference method (NGSP laboratory) and the CAPI 3 Hb A1c. The results show low relative % bias from the reference method for these variants across different HbA1c concentrations (e.g., Hb S: 1.6% at ~6.5%, 2.9% at ~9%; Hb C: -1.8% at ~6.5%, 3.9% at ~9%; Hb D: 1.0% at ~6.5%, 0.8% at ~9%; Hb E: 1.5% at ~6.5%, 1.2% at ~9%; Hb A2: 0.7% at ~6.5%, 0.4% at ~9%). "No interference has been observed with HbA1c fraction quantification due to the presence of major abnormal hemoglobins Hb S (≤ 40.8 %), Hb C (≤ 37.6 %), Hb D (≤ 41.3 %) and Hb E (≤ 26.8 %)."
6. Warning statement for HbF or other low-frequency variants (if applicable): When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all the labeling material for these devices describing the interference and any affected population.	g. Interferences: "A significant negative interference has been observed with fetal hemoglobin (HbF) concentrations > 23%. HbA1c results are invalid for patients with high amounts of HbF (>23%) including those with known Hereditary Persistence of Fetal Hemoglobin." (Implies this will be addressed in labeling, as per acceptance criteria).

2. Sample Size Used for the Test Set and Data Provenance

Precision/Reproducibility Study (Section 5a):
- Sample Size: Four different whole blood samples at specific targeted HbA1c concentrations (~5%, ~6.5%, ~8%, ~12%) were used. These were analyzed in duplicate on two capillaries per run on 3 instruments. The study used three lots of kits over 24 days, resulting in a total of 1728 individual results.
- Data Provenance: The document does not explicitly state the country of origin for these samples. It implies they are clinical samples used in a laboratory setting for reproducibility testing within the manufacturer's or contracted facility. The study design (CLSI guidelines EP05-A3) suggests a prospective, experimentally controlled setup.
Comparison Studies (Accuracy) (Section 5e):
- Sample Size: 152 variant-free whole blood samples.
- Data Provenance: The samples covered the measuring range and spanned decision points for diabetes diagnosis. The comparison was against results from an NGSP reference laboratory using a cleared HPLC HbA1c method. The specific origin (e.g., country) or whether these were retrospectively or prospectively collected is not stated, but the nature of a comparison study with a reference method implies a real-world clinical sample set.
Interference Studies (Section 5g):
- Sample Size: Two different whole blood samples (one near cut-off, one with elevated HbA1c) were used for endogenous and drug interference testing. For hemoglobin variant interference, a number of specific samples were used (e.g., 20 Hb A2 samples, 19 Hb F samples, 24 each for Hb S, C, D, and E samples).
- Data Provenance: Not explicitly stated regarding country or retrospective/prospective. The description suggests these were specific, characterized samples obtained for interference testing, likely in a controlled laboratory environment.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

For this in-vitro diagnostic device (HbA1c measurement), "ground truth" is typically established by reference methods or standardized laboratory procedures, not by expert consensus in the way imaging AI models are.
Comparison Study (Section 5e): The ground truth for the 152 samples was established by "testing performed at a NGSP reference laboratory using the cleared HPLC HbA1c method (Automated Glycohemoglobin Analyzer HLC-712G8)." This is the gold standard for HbA1c measurement and implies the highest level of analytical accuracy for the measured values.
The document does not mention human experts establishing ground truth or their qualifications; it relies on a technical reference standard.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in subjective interpretation tasks (e.g., radiology image reading) where multiple human readers contribute to a consensus ground truth.
For quantitative lab tests like HbA1c, adjudication is not applicable in the same sense. The "ground truth" is the result obtained from a single, highly accurate, standardized reference method, which is considered definitive. Any comparison is statistical, typically regressing one device's results against the reference method's results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done.
MRMC studies are relevant for medical imaging devices where human readers interpret images, and the AI system is an "assistant" in that interpretive task.
This device is an automated in-vitro diagnostic assay, meaning it directly measures a biomarker. It's not an AI system designed to assist human interpretation of complex visual data. Therefore, the concept of "human readers improving with AI vs. without AI assistance" does not apply here.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Yes, the primary performance shown is "standalone" performance.
The CAPI 3 Hb A1c kit, when run on the CAPILLARYS 3 TERA instrument, provides a direct quantitative measurement. The performance data presented (precision, linearity, comparison, total error, interferences) are all reflective of the device's analytical performance on its own, without human real-time intervention for result calculation or interpretation beyond standard laboratory procedures for operating the instrument and reporting results.
The output is a numerical value (%HbA1c or mmol/mol), not an image or diagnosis requiring human interpretation in the loop with an AI algorithm.

7. Type of Ground Truth Used

The ground truth for the comparison studies (accuracy) was established by a standardized reference method (HPLC HbA1c) run at an NGSP reference laboratory.
This is a form of analytical reference standard, considered the most accurate and reliable method for determining true HbA1c concentrations in the samples.
For precision and interference studies, the "ground truth" is inherent to the specific sample concentrations being tested, often prepared or characterized against
these same reference methodologies.

8. Sample Size for the Training Set

This information is not provided because this is not an AI/ML (Artificial Intelligence/Machine Learning) device requiring a "training set."
The CAPI 3 Hb A1c kit is an in-vitro diagnostic device based on the principle of capillary electrophoresis, a well-established analytical chemistry technique. Its "performance" is governed by its chemical reagents, instrument design, and physical principles, not by a learned algorithm from data.
Therefore, there is no "training set" in the context of machine learning. The development and validation of such a device involve optimization of reagents, hardware, and software parameters, followed by rigorous analytical performance validation studies (as detailed in Section 5).

9. How the Ground Truth for the Training Set was Established

Not applicable, as there is no "training set" for this type of device (see point 8 above).

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

September 12, 2017

SEBIA, INC. KAREN ANDERSON DIRECTOR OF TECHNICAL AND QUALITY ASSURANCE 1705 CORPORATE DRIVE SUITE 400 NORCROSS GA 30093

Re: K171537

Trade/Device Name: CAPI 3 Hb A1c Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c Test System Regulatory Class: II Product Code: PDJ Dated: July 24, 2017 Received: July 27, 2017

Dear Ms. Karen Anderson:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney H. Lias -S

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K171537

Device Name CAPI 3 Hb A1c

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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510K SUMMARY (Summary of Safety and Effectiveness) - K171537

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

Submitter Name	Sebia, Inc.
Address	1705 Corporate Drive Suite 400Norcross, Georgia 30093, USA
Contact	Karen Anderson, Dir of Technical and QAPhone: 1-800-835-6497Fax: 770-446-8511Email: karen.anderson@sebia-usa.comAigars Brants, Ph.D, Scientific Affairs OfficerPhone 1-800-835-6497Fax 770-446-8511Email: aigars.brants@sebia-usa.com
Date Prepared	August 14, 2017
Manufacturing	SebiaParc Technologique Léonard de VinciRue Léonard de Vinci,CP 8010 LISSES, 91008 EVRY CedexFRANCEPhone: (33) 1 69 89 80 80Fax: (33) 1 69 89 78 78
Product Name	CAPI 3 Hb A1c
Common Name	Whole blood hemoglobin A1c (HbA1c) by capillaryelectrophoresis
Product Regulation No.	21 CFR 862.1373
Product Codes	PDJ
Device classification and PanelClassification	Class II , Clinical Chemistry(75)
Establishment Registration No.	8023024

510(k) Summary 1

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1. DEVICE DESCRIPTION

The CAPILLARYS 3 TERA instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses of HbA1c quantification in a whole blood sample. A sample dilution with hemolysing solution is prepared and injected by aspiration at the anodic end of the capillary. A high voltage protein separation is then performed and direct detection of the hemoglobins is made at the cathodic end of the capillary at 415 nm, which is the absorbance wave length specific to hemoglobins. Before each run, the capillaries are washed with a wash solution and prepared for the next analysis with buffer.

Direct detection provides accurate relative quantification of individual hemoglobin A1c fraction. In addition, the high resolution of CAPI 3 Hb A1c procedure allows the quantification of HbA1c even in the presence of labile HbA1c. carbamylated and acetylated hemoglobins, and major hemoqlobin variants.

By using an alkaline pH buffer, normal and abnormal (or variant) hemoglobins are detected in the following order, from cathode to anode: A2/C, E, S/D, F, A0, other Hb (including minor Hb A1) and then A1c.

The HbA1c concentrations are standardized and indicated in %HbA1c (DCCT/NGSP) and in mmol/mol (IFCC) units.

Reagents:

CAPI 3 Hb A1c KIT

ITEMS	PN 2515
Buffer (ready to use)	2 vials, 700 mL each
Hemolysing solution (ready to use)	1 vial, 700 mL
Filters	4 filters

Additional reagents not included in the CAPI 3 Hb A1c KIT

ITEMS	PN	COMPONENTS
CAPICLEAN CAPILLARYS 3	2060	1 vial, 25 mL
CAPILLARYS 3 WASH SOLUTION	2062	1 vial, 75mL

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CAPI 3 DISPOSABLES KIT	2580	10 packs of 14 reagent cups5 bins for used reagent cups
TEST TUBES	9214	200 of 100 mm-tubes
CAPI 3 BINS FOR USED REAGENTCUPS	2581	5 units
TUBES AND CAPS FOR	9202	20 units
CONTROLS	9205	500 units
CAPI 3 REAGENT CUPS	2582	24 packs of 14 reagent cups

2. INDICATIONS FOR USE

CAPI 3 Hb A1c kit:

The CAPI 3 Hb A1c kit is intended for separation and quantification of the HbA1c glycated fraction of hemoglobin (in IFCC unit (mmol/mol) and NGSP unit (%)) in venous whole human blood, by capillary electrophoresis in alkaline buffer with the CAPILLARYS 3 TERA instrument. Measurement of hemoglobin A1c is used as an aid in diagnosis of diabetes, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of longterm blood glucose control in individuals with diabetes mellitus. The CAPI 3 Hb A1c kit is intended for in vitro Diagnostic Use Only.

3. TECHNOLOGICAL CHARACTERISTICS

The CAPILLARYS 3 TERA instrument uses the principle of capillary electrophoresis in free solution which is the most common form of capillary electrophoresis. With this technique, charged molecules are separated by their electrophoretic mobility in an alkaline buffer with a specific pH. Separation also occurs according to the electrolyte pH and electroosmotic flow.

The CAPILLARYS 3 TERA instrument has silica capillaries functioning in parallel allowing 12 simultaneous analyses of Hb A1c quantification in a whole blood sample. A sample dilution with hemolysing solution is prepared and injected by aspiration at the anodic end of the capillary. A high voltage protein separation is then performed and direct detection of the hemoglobins is made at the cathodic end of the capillary at 415 nm, which is the absorbance wave length specific to hemoglobins. Before each run, the capillaries are washed with a wash solution and prepared for the next analysis with buffer.

Direct detection provides accurate relative quantification of individual hemoglobin A1cfraction. In addition, the high resolution of CAPI 3 Hb A1c procedure allows the quantification of HbA1c, and particularly, even in the presence of labile HbA1c, carbamylated and acetylated hemoglobins, and major hemoglobin variants.

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4. SUBSTANTIAL EQUIVALENCE INFORMATION:

Predicate Device Name	Predicate Device510(k) number	Product Code	Regulation No
Tosoh AutomatedGlycohemoglobin Analyzer HLC-723G-8	K131580	PDJ	862.1373

Similarities between the candidate device (CAPI 3 Hb A1c) and the predicate device (Tosoh HLC-723G8, K131580 (Table A).

	Similarities
Table A	Sebia CAPI 3 Hb A1c CandidateDevice	Tosoh HLC-723G8 PredicateDevice (K131580)
Intended use	The CAPI 3 Hb A1c kit is intended forseparation and quantification of the HbA1cglycated fraction of hemoglobin (in IFCC unit(mmol/mol) and NGSP unit (%)) in venouswhole human blood, by capillaryelectrophoresis in alkaline buffer with theCAPILLARYS 3 TERA instrument.Measurement of hemoglobin A1c is used asan aid in diagnosis of diabetes, as an aid toidentify patients who may be at risk fordeveloping diabetes mellitus, and for themonitoring of long-term blood glucose controlin individuals with diabetes mellitus. The CAPI3 Hb A1c kit is intended for in vitro DiagnosticUse Only.	The Tosoh AutomatedGlycohemoglobin AnalyzerHLC723G8 is intended for the in vitrodiagnostic use for the measurement of% hemoglobin A1c (HbA1c)(DCCT/NGSP) and mmol/molhemoglobin A1c (IFCC) in wholeblood specimens. This test is to beused as an aid in diagnosis ofdiabetes and identifying patients whomay be at risk of developing diabetes.
Specimen Type	Human Whole Blood	Human Whole Blood
Standardization	Traceable to the Diabetes Control andComplications Trial (DCCT) referencemethod and IFCC. Certified via the NationalGlycohemoglobin Standardization Program (NGSP)	Same
LinearityMeasuring Range	4.0 - 16.5% (NGSP)20 - 157 mmol/mol (IFCC)	4.0 - 16.9 %

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	Concentration	TE%	Concentration	TE%
Total Errorallowable bias 6%	5.2	4.4	5.0	5.8
	6.5	2.9	6.5	2.8
	8.1	2.3	8.0	3.0
	11.9	3.6	12.0	3.1
HemoglobinVariantInterferences	HbA2, HbF, HbS, HbC, HbD,does not interfere with this assay			HbA2, HbF, HbS, HbC, HbD, doesnot interfere with this assay

Table B. Differences between the predicate device (CAPI 3 Hb A1c) and the candidate device (Tosoh HLC-723G8, K131580) in (Table B).

	Differences
Table B	Sebia CAPI 3 Hb A1cCandidate Device	Tosoh HLC-723G8Predicate Device (K131580)
Assay Principle	Capillary electrophoresis	Ion-exchange HPLC
HemoglobinVariantInterferences	Hb E no interference	Hb E has known interference, a HbEflag is displayed and no Hb A1c isreported.

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5. Performance Data:

a. Precision / Reproducibility:-

The precision of the CAPI 3 Hb A1c procedure using the CAPILLARYS 3 TERA was evaluated based on CLSI guidelines EP05-A3 guidelines, Evaluation of Quantitative Measurement Procedures. Four whole blood samples at the following targeted HbA1c concentration of ~ 5%, ~ 6.5%, ~ 8%, and ~12% were used in the study. The study included two quality control materials and two calibrators. The samples were analyzed in duplicate on two capillaries per run on 3 instruments. The studied used three lots of kits over 24 days yielding a total of 1728 results over total testing time of 72 days.

Sample	Mean(mmol/mol)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Betweeninstrument		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No.1	33	0,50	1,5%	0,48	1,4%	0,00	0,0%	0,24	0,7%	0,40	1,2%	0,18	0,6%	0,86	2,6%
Sample No.2	34	0,49	1,4%	0,52	1,5%	0,00	0,0%	0,28	0,8%	0,49	1,5%	0,00	0,0%	0,91	2,7%
Sample No.3	37	0,44	1,2%	0,51	1,4%	0,00	0,0%	0,27	0,7%	0,42	1,1%	0,00	0,0%	0,84	2,3%
Sample No.4	48	0,56	1,2%	0,43	0,9%	0,26	0,5%	0,22	0,5%	0,38	0,8%	0,00	0,0%	0,83	1,7%
Sample No.5	61	0,53	0,9%	0,43	0,7%	0,00	0,0%	0,43	0,7%	0,09	0,1%	1,52	2,6%	1,72	2,9%
Sample No.6	65	0,62	1,0%	0,43	0,7%	0,00	0,0%	0,31	0,5%	0,23	0,4%	0,13	0,2%	0,86	1,3%
Sample No.7	86	0,64	0,7%	0,49	0,6%	0,00	0,0%	0,39	0,5%	0,72	0,8%	0,00	0,0%	1,14	1,3%
Sample No.8	107	0,74	0,7%	0,83	0,8%	0,00	0,0%	0,67	0,6%	1,79	1,7%	0,00	0,0%	2,21	2,1%

(*) Total reproducibility includes : within-capillary, between-run, between-day, between-lot and between-instrument.

Sample	Mean	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Betweeninstrument		Totalreproducibility(*)
	(%)	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No.1	5,2	0,05	0,9%	0,04	0,8%	0,00	0,0%	0,02	0,4%	0,04	0,7%	0,02	0,3%	0,08	1,5%
Sample No.2	5,2	0,05	0,9%	0,05	0,9%	0,00	0,0%	0,03	0,6%	0,04	0,7%	0,00	0,0%	0,08	1,6%
Sample No.3	5,5	0,04	0,8%	0,04	0,8%	0,00	0,0%	0,03	0,5%	0,04	0,7%	0,00	0,0%	0,08	1,4%
Sample No.4	6,5	0,05	0,7%	0,04	0,5%	0,02	0,3%	0,02	0,3%	0,03	0,5%	0,00	0,0%	0,07	1,1%
Sample No.5	7,7	0,05	0,7%	0,04	0,5%	0,00	0,0%	0,04	0,5%	0,01	0,2%	0,13	1,7%	0,15	2,0%
Sample No.6	8,1	0,06	0,7%	0,04	0,5%	0,00	0,0%	0,03	0,4%	0,02	0,3%	0,01	0,1%	0,08	1,0%
Sample No.7	10,1	0,06	0,6%	0,05	0,5%	0,00	0,0%	0,04	0,4%	0,07	0,7%	0,00	0,0%	0,11	1,1%
Sample No.8	11,9	0,07	0,6%	0,08	0,6%	0,00	0,0%	0,06	0,5%	0,16	1,4%	0,00	0,0%	0,20	1,7%

(*) Total reproducibility includes : within-capillary, between-cay, between-day, between-ot and between-instrument.

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The reproducibility within the same instrument is summarized in the following tables:

including within-capillary, between-capillary, between-run, between-day, between-lot and total reproducibility precision estimates (SD and %CV) for the HbA1c concentrations (in mmol/mol) and percentages for each instrument.
including the within-lot precision estimates (SD and %CV) for the HbA10 concentrations -(in mmol/mol) and percentages for each lot on each instrument.

Sample	Mean(mmol/mol)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No. 1	33	0,50	1,5%	0,42	1,3%	0,00	0,0%	0,19	0,6%	0,42	1,3%	0,80	2,4%
Sample No. 2	34	0,42	1,3%	0,49	1,4%	0,00	0,0%	0,28	0,8%	0,62	1,8%	0,94	2,8%
Sample No. 3	37	0,47	1,3%	0,44	1,2%	0,00	0,0%	0,30	0,8%	0,45	1,2%	0,84	2,3%
Sample No. 4	48	0,55	1,1%	0,38	0,8%	0,18	0,4%	0,28	0,6%	0,49	1,0%	0,89	1,9%
Sample No. 5	61	0,51	0,9%	0,50	0,8%	0,00	0,0%	0,37	0,6%	0,07	0,1%	0,81	1,4%
Sample No. 6	65	0,59	0,9%	0,38	0,6%	0,00	0,0%	0,34	0,5%	0,38	0,6%	0,86	1,3%
Sample No. 7	86	0,73	0,8%	0,47	0,5%	0,00	0,0%	0,44	0,5%	1,00	1,2%	1,39	1,6%
Sample No. 8	107	0,70	0,6%	0,76	0,7%	0,00	0,0%	0,70	0,6%	2,41	2,2%	2,71	2,5%

Instrument No. 1

(*) Total reproducibility includes : within-capillary, between-run, between-run, between-day and between-lot.

Sample	Mean (mmol/mol)	Within-lot (*)
		Lot No. 1		Lot No. 2		Lot No. 3
		SD	CV	SD	CV	SD	CV
Sample No. 1	33	0,67	2,0%	0,62	1,9%	0,75	2,3%
Sample No. 2	34	0,72	2,1%	0,75	2,3%	0,65	1,9%
Sample No. 3	37	0,65	1,8%	0,70	1,9%	0,77	2,1%
Sample No. 4	48	0,80	1,7%	0,78	1,6%	0,70	1,5%
Sample No. 5	61	0,97	1,6%	0,60	1,0%	0,83	1,4%
Sample No. 6	65	0,76	1,2%	0,64	1,0%	0,93	1,4%
Sample No. 7	86	0,98	1,2%	0,72	0,8%	1,16	1,3%
Sample No. 8	107	1,33	1,3%	1,20	1,1%	1,25	1,2%

(*) Within-lot reproducibility includes : within-capillary, between-run and between-day.

Sample	Mean(%)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No. 1	5,2	0,04	0,9%	0,04	0,8%	0,00	0,0%	0,02	0,4%	0,04	0,8%	0,08	1,5%
Sample No. 2	5,2	0,04	0,8%	0,05	0,9%	0,00	0,0%	0,03	0,6%	0,05	0,9%	0,08	1,6%
Sample No. 3	5,5	0,05	0,8%	0,05	0,9%	0,00	0,0%	0,04	0,7%	0,04	0,7%	0,09	1,6%
Sample No. 4	6,5	0,05	0,7%	0,04	0,6%	0,02	0,3%	0,02	0,2%	0,05	0,7%	0,08	1,2%
Sample No. 5	7,7	0,05	0,6%	0,04	0.6%	0,00	0,0%	0,03	0,4%	0,01	0.1%	0,07	0,9%
Sample No. 6	8,1	0,06	0,7%	0,04	0,5%	0,00	0,0%	0,03	0,4%	0,03	0,4%	0,08	1,0%
Sample No. 7	10,1	0,06	0,6%	0,04	0,4%	0,00	0,0%	0,04	0,4%	0,10	1,0%	0,13	1,3%
Sample No. 8	11,9	0,07	0,6%	0,07	0,6%	0,00	0,0%	0,06	0,5%	0,21	1,8%	0,24	2,0%

510(k) Summary 7

{10}------------------------------------------------

(*) Total reproducibility includes : within-capillary, between-run, between-run, between-day and between-lot.

Sample	Mean (%)	Within-lot (*)
		Lot No. 1		Lot No. 2		Lot No. 3
		SD	CV	SD	CV	SD	CV
Sample No. 1	5,2	0,06	1,1%	0,07	1,3%	0,07	1,4%
Sample No. 2	5,2	0,06	1,2%	0,08	1,6%	0,06	1,2%
Sample No. 3	5,5	0,07	1,3%	0,07	1,4%	0,08	1,4%
Sample No. 4	6,5	0,07	1,1%	0,06	0,9%	0,07	1,0%
Sample No. 5	7,7	0,09	1,1%	0,06	0,8%	0,07	0,9%
Sample No. 6	8,1	0,08	0,9%	0,06	0,7%	0,09	1,1%
Sample No. 7	10,1	0,09	0,9%	0,08	0,8%	0,09	0,9%
Sample No. 8	11,9	0,12	1,0%	0,11	0,9%	0,12	1,0%

(*) Within-lot reproducibility includes : within-capillary, between-run and between-day.

Instrument No. 2

Sample	Mean(mmol/mol)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No. 1	33	0,57	1,7%	0,55	1,7%	0,00	0,0%	0,22	0,7%	0,45	1,4%	0,94	2,8%
Sample No. 2	34	0,54	1,6%	0,56	1,7%	0,00	0,0%	0,24	0,7%	0,42	1,3%	0,91	2,7%
Sample No. 3	37	0,45	1,2%	0,53	1,5%	0,00	0,0%	0,23	0,6%	0,31	0,8%	0,80	2,2%
Sample No. 4	48	0,61	1,3%	0,41	0,9%	0,37	0,8%	0,15	0,3%	0,30	0,6%	0,89	1,9%
Sample No. 5	61	0,55	0,9%	0,28	0,5%	0,00	0,0%	0,48	0,8%	0,00	0,0%	0,78	1,3%
Sample No. 6	65	0,69	1,1%	0,34	0,5%	0,00	0,0%	0,31	0,5%	0,03	0,0%	0,83	1,3%
Sample No. 7	86	0,58	0,7%	0,55	0,6%	0,00	0,0%	0,40	0,5%	0,41	0,5%	0,99	1,1%
Sample No. 8	107	0,81	0,8%	1,01	0,9%	0,00	0,0%	0,76	0,7%	1,38	1,3%	2,04	1,9%

(*) Total reproducibility includes : within-capillary, between-run, between-day and between-lot.

Sample	Mean(mmol/mol)	Within-lot (*)
		Lot No. 1		Lot No. 2		Lot No. 3
		SD	CV	SD	CV	SD	CV
Sample No. 1	33	0,88	2,6%	0,73	2,2%	0,84	2,5%
Sample No. 2	34	0,88	2,6%	0,65	2,0%	0,90	2,7%
Sample No. 3	37	0,87	2,4%	0,56	1,5%	0,74	2,0%
Sample No. 4	48	0,79	1,7%	0,89	1,9%	0,86	1,8%
Sample No. 5	61	0,66	1,1%	0,67	1,1%	0,98	1,6%
Sample No. 6	65	0,75	1,2%	0,77	1,2%	0,99	1,5%
Sample No. 7	86	1,03	1,2%	0,79	0,9%	0,86	1,0%
Sample No. 8	107	1,73	1,6%	1,45	1,4%	1,47	1,4%

(*) Within-lot reproducibility includes : within-capillary, between-run and between-day.

{11}------------------------------------------------

Sample	Mean(%)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No. 1	5,2	0,05	1,0%	0,05	0,9%	0,00	0,0%	0,02	0,4%	0,05	0,9%	0,09	1,7%
Sample No. 2	5,2	0,05	0,9%	0,06	1,1%	0,00	0,0%	0,02	0,4%	0,03	0,7%	0,09	1,6%
Sample No. 3	5,5	0,04	0,8%	0,04	0,8%	0,00	0,0%	0,02	0,4%	0,04	0,8%	0,08	1,4%
Sample No. 4	6,5	0,05	0,7%	0,03	0,5%	0,02	0,3%	0,02	0,4%	0,02	0,4%	0,07	1,1%
Sample No. 5	7,7	0,05	0,7%	0,03	0,3%	0,00	0,0%	0,05	0,6%	0,01	0,1%	0,08	1,0%
Sample No. 6	8,1	0,07	0,8%	0,03	0,3%	0,01	0,1%	0,03	0,3%	0,01	0,1%	0,08	0,9%
Sample No. 7	10,1	0,05	0,5%	0,05	0,5%	0,00	0,0%	0,03	0,3%	0,05	0,5%	0,10	1,0%
Sample No. 8	11,9	0,08	0,6%	0,09	0,8%	0,02	0,2%	0,07	0,6%	0,13	1,1%	0,19	1,6%

(*) Total reproducibility includes : within-capillary, between-run, between-day and between-lot.

Sample	Mean (%)	Within-lot (*)
		Lot No. 1		Lot No. 2		Lot No. 3
		SD	CV	SD	CV	SD	CV
Sample No. 1	5,2	0,08	1,5%	0,06	1,2%	0,08	1,6%
Sample No. 2	5,2	0,09	1,7%	0,07	1,3%	0,08	1,6%
Sample No. 3	5,5	0,06	1,2%	0,06	1,1%	0,07	1,3%
Sample No. 4	6,5	0,06	1,0%	0,06	1,0%	0,07	1,1%
Sample No. 5	7,7	0,06	0,8%	0,06	0,8%	0,10	1,2%
Sample No. 6	8,1	0,07	0,8%	0,08	0,9%	0,09	1,1%
Sample No. 7	10,1	0,10	1,0%	0,07	0,7%	0,08	0,8%
Sample No. 8	11,9	0,15	1,3%	0,14	1,2%	0,14	1,2%

(*) Within-lot reproducibility includes : within-capillary, between-run and between-run and between-day.

Instrument No. 3

Sample	Mean(mmol/mol)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No. 1	33	0,44	1,3%	0,46	1,4%	0,00	0,0%	0,30	0,9%	0,33	1,0%	0,77	2,3%
Sample No. 2	34	0,49	1,4%	0,50	1,5%	0,00	0,0%	0,32	0,9%	0,40	1.2%	0,87	2,6%
Sample No. 3	37	0,40	1,1%	0,54	1,5%	0,00	0,0%	0,29	0,8%	0,48	1,3%	0,88	2,4%
Sample No. 4	48	0,52	1,1%	0,49	1,0%	0,17	0,4%	0,21	0,4%	0,32	0,7%	0,83	1,7%
Sample No. 5	61	0,54	0,9%	0,46	0,7%	0,00	0,0%	0,42	0,7%	0,15	0,2%	0,84	1,3%
Sample No. 6	65	0,59	0,9%	0,55	0,8%	0,00	0,0%	0,28	0,4%	0,12	0,2%	0,86	1,3%
Sample No. 7	86	0,58	0,7%	0,45	0,5%	0,00	0,0%	0,31	0,4%	0,61	0,7%	1,01	1,2%
Sample No. 8	107	0.69	0,6%	0,68	0,6%	0,00	0,0%	0,53	0,5%	1,39	1,3%	1,77	1,7%

(*) Total reproducibility includes : within-capillary, between-run, between-day and between-lot.

{12}------------------------------------------------

Sample	Mean (mmol/mol)	Within-lot (*)
		Lot No. 1		Lot No. 2		Lot No. 3
		SD	CV	SD	CV	SD	CV
Sample No. 1	33	0,61	1,8%	0,89	2,7%	0,57	1,7%
Sample No. 2	34	0,64	1,9%	1,00	3,0%	0,59	1,7%
Sample No. 3	37	0,53	1,4%	0,94	2,6%	0,67	1,8%
Sample No. 4	48	0,72	1,5%	0,88	1,8%	0,74	1,5%
Sample No. 5	61	0,78	1,2%	0,87	1,4%	0,83	1,3%
Sample No. 6	65	0,71	1,1%	0,88	1,4%	0,96	1,5%
Sample No. 7	86	0,69	0,8%	0,76	0,9%	0,93	1,1%
Sample No. 8	107	1,09	1,0%	1,16	1,1%	1,09	1,0%

(*) Within-lot reproducibility includes : within-capillary, between-run and between-day.

Sample	Mean(%)	Within-capillary		Betweencapillary		Between-run		Between-day		Between-lot		Totalreproducibility(*)
		SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
Sample No. 1	5,2	0,05	0,9%	0,04	0,8%	0,00	0,0%	0,03	0,5%	0,01	0,2%	0,07	1,3%
Sample No. 2	5,2	0,05	0,9%	0,04	0,8%	0,00	0,0%	0,03	0,6%	0,03	0,6%	0,08	1,5%
Sample No. 3	5,5	0,04	0,8%	0,04	0,7%	0,00	0,0%	0,02	0,4%	0,04	0,7%	0,07	1,3%
Sample No. 4	6,5	0,05	0,8%	0,04	0,6%	0,02	0,4%	0,02	0,2%	0,03	0,4%	0,07	1,1%
Sample No. 5	7,7	0,05	0,6%	0,04	0,6%	0,00	0,0%	0,03	0,4%	0,02	0,3%	0,08	1,0%
Sample No. 6	8,1	0,06	0,7%	0,05	0,6%	0,00	0,0%	0,03	0,4%	0,01	0,1%	0,08	1,0%
Sample No. 7	10,1	0,05	0,5%	0,04	0,4%	0,00	0,0%	0,03	0,3%	0,06	0,6%	0,10	1,0%
Sample No. 8	11,9	0,06	0,5%	0,07	0,6%	0,00	0,0%	0,05	0,4%	0,13	1,1%	0,17	1,4%

(*) Total reproducibility includes : within-capillary, between-run, between-run, between-lot.

Sample	Mean(%)	Within-lot (*)
		Lot No. 1		Lot No. 2		Lot No. 3
		SD	CV	SD	CV	SD	CV
Sample No. 1	5,2	0,05	1,0%	0,09	1,6%	0,06	1,2%
Sample No. 2	5,2	0,06	1,2%	0,09	1,7%	0,06	1,2%
Sample No. 3	5,5	0,05	0,9%	0,08	1,4%	0,06	1,1%
Sample No. 4	6,5	0,07	1,0%	0,08	1,2%	0,06	1,0%
Sample No. 5	7,7	0,07	0,9%	0,08	1,0%	0,07	0,9%
Sample No. 6	8,1	0,07	0,9%	0,08	1,0%	0,09	1,2%
Sample No. 7	10,1	0,06	0,6%	0,07	0,7%	0,10	0,9%
Sample No. 8	11,9	0,11	0,9%	0,11	0,9%	0,10	0,9%

(*) Within-lot reproducibility includes : within-capillary, between-run and between-day.

{13}------------------------------------------------

b. Linearity / assay reportable range

A linearity study was performed per CLSI EP06-A: Evaluation of Quantitative Measuring Procedures: A Statistical Approach, Linearity across the reportable range was performed using low 3.8% Hb A1c (18 mmol/mol) and high 17.3% (166 mmol/mol).

Mixture of 2 different blood samples:

2 characteristic blood samples, including a normal sample and an elevated HbA10 level sample were mixed within different proportions and the mixtures were electrophoresed with the CAPI 3 Hb A1c procedure. For each mixture, samples were analyzed in triplicate.

The tests were determined to be linear within the entire range studied for HbA% hemoglobin fraction. The stated measuring range is 20 mmol/mol to 157 mmol/mol HbA+c (4.0 % to 16.5 % HbA1c).

Dilution of 4 different blood samples in hemolysing solution :

4 different characteristic blood samples, including 1 normal sample with HbA1c concentration at 21 mmol/mol (4.1 % HbA1c), 1 sample with HbA1c level close to the cut-off value with HbA1c concentration at 47 mmol/mol (6.4 % HbA1c) and 2 elevated HbA1c level samples with HbA1c concentrations at 82 mmol/mol (9.6 % HbA1c) and at 134 mmol/mol (14.4 % HbA1c), were all serially diluted in hemolysing solution and electrophoresed with the CAPI 3 Hb A1c procedure. The tests were determined to be linear within the entire ranges studied from 2.9 to 30.5 g/dL total hemoglobin and HbA1c fraction concentration and percentage were not affected by the hemoglobin concentration of the samples.

c. Traceability, Stability (controls, calibrators, or methods)

The CAPI 3 Hb A1c test standardization is traceable to the International Federation of Clinical Chemistry (IFCC) reference calibrators.

The CAPI 3 Hb A1c assay is NGSP certified. The NGSP certification expires in one year. See the NGSP website for current certification at http://www.ngsp.org

Hb A1c results are provided in two different units: NGSP equivalent units (%) and IFCC equivalent units (mmol/mol).

d. Calibrators and Controls

The Hb A1c CAPILLARY CALIBRATORS are required for use with this device. Value assignment and stability protocal and acceptance criteria were previously reviewed and cleared in K162281 and K122101.

Sebia MULTI-SYSTEM Hb A1c CAPILLARYS CONTROLS are required for use with this device and cleared in submission K162281.

{14}------------------------------------------------

e. Comparison Studies

A method comparison study of 152 variant-free whole blood samples covering the measuring range were evaluated using the Capi3 Hb A1c kit and the CAPILLARYS 3 TERA instrument. The results were compared to the testing performed at a NGSP reference laboratory using the cleared HPLC HbA1c method (Automated Glycohemoglobin Analyzer HLC-712G8).

To support the diagnostic claim for HbA1c the samples spanned around the decision points as follows:

HbA1c level	Number of samples	% of samples
HbA1c ≤ 5 %	9	6
5,0 % < HbA1c ≤ 6,0 %	19	13
6,0 % < HbA1c ≤ 6,5 %	35	23
6,5 % < HbA1c ≤ 7,0 %	36	24
7,0 % < HbA1c ≤ 8,0 %	23	15
8,0 %< HbA1c ≤ 9,0 %	13	9
HbA1c > 9,0 %	17	11
Total	152	100

HbA1c results given as a NGSP unit (%)

Fraction	Correlation coefficient	y-intercept	Slope	Range of HbA1c % valuesCAPI 3 Hb A1c
HbA1c	0,999	-0,142	1,014	3,9 - 16,5

152 samples

Regression Analysis (HbA1c fraction)
Ordinary line ar fit
95 % Confidence Intervals are shown in parentheses
Points (Plotted/Total)	152/152
Results Ranges	3,9 to 16,5
Normal range	< 6,5
Correlation coefficient (r)	0,999
Slope	1,014 (1,007 to 1,021)
y-intercept	-0,142 (-0,197 to -0,087)
Average bias (all samples)	-0,04 (-0,06 to -0,02)
Bias at normal range	The bias at 6,5 is -0,05 (-0,07 to -0,03)

The unit of the bias is the same of the result provided (%)

{15}------------------------------------------------

f. Total Error Calculations

Total error (TE) is calculated for 4 concentrations, corresponding to the concentrations of the samples used in the reproducibility study, (5.2 %, 6.5 %, 8.1 % and 11.9 %) using the results of bias estimation (%Bias) and coefficients of variation (CV).

Total Error is calculated as follows: %TE=|%Bias| + 1.96 CV (1 + %Bias/100)).

The results are presented in the following table for the CAPI3 Hb A1c using the CAPILLARYS 3 TERA instrument:

Linear equationregression	Target (%)	y from linearequation	Deviation fromtarget	%Bias	CV (%)	TE (%)	Specification
$y = 1,014 x -0,142$	5,2	5,1	-0,1	-1,32	1,6	4,4	≤ 6,0 %
	6,5	6,4	-0,1	-0,77	1,1	2,9
	8,1	8,1	0,0	-0,34	1,0	2,3
	11,9	11,9	0,0	0,22	1,7	3,6

HbA1c results given as a NGSP unit (%)

g. Interferences

Interference studies were performed per CLSI EP07-A2, Interference Testing in Clinical Chemistry. Each study was performed using 2 different whole blood samples: a blood sample close to the cut-off value and a blood sample with elevated HbA1c level. Ten replicates were analyzed using the CAPI 3 Hb A1c on the CAPILLARYS 3 TERA testing system.

No interference with the CAPI 3 Hb A1c procedure was detected due to the blood sample's high concentration of the following interfering factors tested at levels equal to the concentrations listed below:

Endogenous interfering factor	Concentration
Bilirubin	70 mg/dL (1197 µM)
D-glucose	1000 mg/dL (55 mM)
Glycated Albumin	2.2 mg/mL
Rheumatoid factor	1294 IU/mL
Total Protein	149.5 g/L
Triglycerides	3.58 g/dL (40.9 mM)
Urea	265 mg/dL (44.2 mM)

Drug	Concentration
Acetaminophen	200 mg/L (1325 μM)
Acetylcysteine	200 mg/dL (12.3 mM)
Acetylsalicilyc acid	1000 mg/dL (55.56 mM)
Ampicillin-Na	1000 mg/dL (28653 μM)
Ascorbic acid	300 mg/dL (17045 μM)
Cefoxitin	2500 mg/dL (58548 μM)
Cyclosporine	5 mg/L

510(k) Summary 13

{16}------------------------------------------------

Doxycycline	50 mg/dL (1123.6 μM)
Glybenclamide	3 mg/dL
Heparin	5000 U/L
Ibuprofen	500 mg/L (2427 μM)
Levodopa	40 mg/dL
Metformin	5 mg/dL
Methyldopa	40 mg/dL (1896 μM)
Metronidazole	200 mg/dL (11696 μM)
Phenylbutazone	400 mg/L
Rifampicin	70 mg/L (85.1 μM)
Theophylline	100 mg/L (556 μM)

Hemoglobin Derivatives and crossreactants	Concentrations
Carbamylated Hemoglobin	≤ 8.1 mg/mL
HbA1a+b	≤ 0.20 mg/mL
Labile HbA1c	≤ 20.0 mg/mL
Acetylated hemoglobin	≤ 4.2 mg/mL
Glycated Albumin	≤ 2.2 mg/mL

Hemoglobin Variant Study was performed using specific samples known to contain hemoglobin variants S, C, E, D, A2 and F. The samples were analyzed with a reference method performed in a NGSP laboratory (reference) and with CAPI 3 Hb A1c procedure on CAPILLARYS 3 TERA instrument (test): percentages of HbA1c fraction. The relative deviation (%) between the reference procedure and the test procedure has been calculated for each sample (see the following tables).

HemoglobinVariants	No.ofSamples	Ranges in %Variant	Range of % HbA1cConcentration
Hb A2	20	4.0-7.8	4.5-11.2
Hb F	19	1.5-23.7	5.1-15.1
Hb S	24	33.0-40.8	4.9-14.7
Hb C	24	25.6-37.6	4.9-12.4
Hb D	24	35.5-41.3	5.2-12.0
Hb E	20	21.1-26.8	4.9-9.6

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The percent relative bias from a reference method (commercially available high-performance liquid chromatography technique for HbAre quantification) at low and high concentrations of HbA1c in each sample is:

HemoglobinVariant	Relative % Bias fromReference Method ~ 6.5 % Hb A1cMean Relative % Bias(Range of % Bias for Hb A1c)	Relative % Bias fromReference Method ~ 9 % Hb A1cMean Relative % Bias(Range of % Bias for Hb A1c)
Hb S	1.6% (0% - 3.2%)	2.9% (1.1% - 5.4%)
Hb C	-1.8% (-3.1% - 0%)	3.9% (3.3% - 4.5%)
Hb D	1.0% (0% - 1.6%)	0.8% (0% - 2.4%)
Hb E	1.5% (-1.5% - 1.6%)	1.2% (0%-2.5%)
Hb A2	0.7% (0%-1.5%)	0.4% (0%-1.1%)
Hb F	-4.1% (-3.3% -4.9 %)	-0.8% (0%-2.0%)

A significant neqative interference has been observed with fetal hemoglobin (HbF) concentrations > 23%. HbA1c results are invalid for patients with high amounts of HbF (>23%) including those with known Hereditary Persistence of Fetal Hemoglobin
Levels of Hb A2 up to 7.8 % in the blood sample do not interfere with HbA1c fraction quantification.
No interference has been observed with HbA1c fraction quantification due to the presence of major abnormal hemoglobins Hb S (≤ 40.8 %), Hb C (≤ 37.6 %), Hb D (≤ 41.3 %) and Hb E (≤ 26.8 %).

h. Expected Values/ Reference Range

Hemoglobin Are expected value range was cited from the American Diabetes Association (Standards of Medical Care in Diabetes 2016, 39 (Suppl 1)). The American Diabetes Association's (ADA) most recent Clinical Practice are:

Category	HbA1c Range (IFCC)	HbA1c Range (NGSP/DCCT)
Normal	< 39 mmol/mol	< 5.7 %
Prediabetes (increased risk fordiabetes)	39 mmol/mol - 47 mmol/mol	5.7 % - 6.4 %
Diabetes	≥ 48 mmol/mol	≥ 6.5 %

The expected HbA ; range for non-diabetic adults is 20 = 42 mmol/mol or 4.0 - 6.0 %. However, each laboratory should establish its reference range and HbA1c goal in their country of business taking into account sex, age, ethnicity and individual patient situation.

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6. Special Controls for Diabetes Diagnosis Claim

YES OR NO	Special Controls
YES	Device must have initial and annual standardization verification bycertifying glycohemoglobin standardization organization deemedacceptable by FDA
YES	Performance testing of device precision must, at a minimum use bloodsamples with concentrations near 5.0%, 6.5%, 8.0% and 12 %hemoglobin A1c. Testing must evaluate precision over a minimum of20 days using at least 3 lots of the device and instruments, asapplicable
YES	Performance testing of accuracy must include a minimum of 120blood samples that span the measuring interval of the new deviceand compare results of the new device to results of the standardizedmethod. Results must demonstrate little or no bias versus thestandardized method.
YES	Total error of the new device must be evaluated using singlemeasurements by the new device compared to the results of thestandardized test method, and this evaluation must demonstrate atotal error of less than or equal to 6%
YES	Performance testing must demonstrate that there is little to nointerference from common hemoglobin variants, includingHemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2 andHemoglobin S.
NA	When assay interference from Hemoglobin F or interference withother hemoglobin variants with low frequency in the population isobserved, a warning statement must be placed in a black box andmust appear in all the labeling material for these devices describingthe interference and any affected population.

7. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Regulation Number and Section

§ 862.1373 Hemoglobin A1c test system.

(a)
Identification. A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA.
(2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following:
(i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable.
(ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method.
(iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent.
(iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
(3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.